rs2307466

Positions:

• chr2-37149171-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135651.3(EIF2AK2):​c.-183-148C>G variant causes a intron change. The variant allele was found at a frequency of 0.0595 in 1,028,280 control chromosomes in the GnomAD database, including 2,119 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.047 (242 hom., cov: 32)
  • Exomes 𝑓: 0.062 (1877 hom.)
• Consequence: EIF2AK2 NM_001135651.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96

Genes affected

EIF2AK2 (HGNC:9437): (eukaryotic translation initiation factor 2 alpha kinase 2) The protein encoded by this gene is a serine/threonine protein kinase that is activated by autophosphorylation after binding to dsRNA. The activated form of the encoded protein can phosphorylate translation initiation factor EIF2S1, which in turn inhibits protein synthesis. This protein is also activated by manganese ions and heparin. The encoded protein plays an important role in the innate immune response against multiple DNA and RNA viruses. [provided by RefSeq, Jul 2021]

ARL14EPP1 (HGNC:54676): (ARL14EP pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2AK2	NM_001135651.3	c.-183-148C>G		intron_variant		ENST00000233057.9	NP_001129123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2AK2	ENST00000233057.9	c.-183-148C>G		intron_variant		2	NM_001135651.3	ENSP00000233057	P2
ARL14EPP1	ENST00000412776.1	n.642G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0468 AC: 7123 AN: 152130 Hom.: 238 Cov.: 32

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0689

Gnomad ASJ AF: 0.0465

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.0941

Gnomad FIN AF: 0.0381

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0629

Gnomad OTH AF: 0.0483

GnomAD4 exome AF: 0.0617 AC: 54055 AN: 876030 Hom.: 1877 Cov.: 13 AF XY: 0.0634 AC XY: 29178 AN XY: 460048

Gnomad4 AFR exome AF: 0.00977

Gnomad4 AMR exome AF: 0.0799

Gnomad4 ASJ exome AF: 0.0480

Gnomad4 EAS exome AF: 0.0121

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.0479

Gnomad4 NFE exome AF: 0.0621

Gnomad4 OTH exome AF: 0.0588

GnomAD4 genome AF: 0.0469 AC: 7137 AN: 152250 Hom.: 242 Cov.: 32 AF XY: 0.0476 AC XY: 3541 AN XY: 74442

Gnomad4 AFR AF: 0.0119

Gnomad4 AMR AF: 0.0691

Gnomad4 ASJ AF: 0.0465

Gnomad4 EAS AF: 0.0158

Gnomad4 SAS AF: 0.0946

Gnomad4 FIN AF: 0.0381

Gnomad4 NFE AF: 0.0629

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0579 Hom.: 37

Bravo AF: 0.0460

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2307466; hg19: chr2-37376314;